Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.14.171 ◽

2018 ◽

Vol 14 ◽

pp. 1961-1971 ◽

Cited By ~ 2

Author(s):

Mohammad A Alnajjar ◽

Jürgen Bartelmeß ◽

Robert Hein ◽

Pichandi Ashokkumar ◽

Mohamed Nilam ◽

...

Keyword(s):

Rational Design ◽

Photophysical Properties ◽

Visible Spectral Region ◽

Correlation Spectroscopy ◽

Binding Motif ◽

Binding Affinities ◽

Binding Motifs ◽

Host Guest Complex ◽

Boron Dipyrromethene ◽

New Applications

We introduce herein boron-dipyrromethene (BODIPY) dyes as a new class of fluorophores for the design of reporter dyes for supramolecular host–guest complex formation with cucurbit[7]uril (CB7). The BODIPYs contain a protonatable aniline nitrogen in the meso-position of the BODIPY chromophore, which was functionalized with known binding motifs for CB7. The unprotonated dyes show low fluorescence due to photoinduced electron transfer (PET), whereas the protonated dyes are highly fluorescent. Encapsulation of the binding motif inside CB7 positions the aniline nitrogen at the carbonyl rim of CB7, which affects the pK a value, and leads to a host-induced protonation and thus to a fluorescence increase. The possibility to tune binding affinities and pK a values is demonstrated and it is shown that, in combination with the beneficial photophysical properties of BODIPYs, several new applications of host–dye reporter pairs can be implemented. This includes indicator displacement assays with favourable absorption and emission wavelengths in the visible spectral region, fluorescence correlation spectroscopy, and noncovalent surface functionalization with fluorophores.

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Theoretical Framework of 1,3-Thiazolium-5-Thiolates Mesoionic Compounds: Exploring the Nature of Photophysical Properties and Molecular Nonlinearity

10.26434/chemrxiv.12063261 ◽

2020 ◽

Author(s):

Zeyu Liu ◽

Shugui Hua ◽

Tian Lu ◽

Ziqi Tian

Keyword(s):

Optical Properties ◽

Rational Design ◽

Rayleigh Scattering ◽

Function Analysis ◽

Theoretical Calculations ◽

Photophysical Properties ◽

Optical Nonlinearity ◽

Nonlinear Properties ◽

Photoelectric Performance ◽

Wave Function Analysis

Inspired by a previous experimental study on the first-order hyperpolarizabilities of 1,3-thiazolium-5-thiolates mesoionic compounds using Hyper-Rayleigh scattering technique, we theoretically investigated the UV-Vis absorption spectra and every order polarizabilities of these mesoionic molecules. Based on the fact that the photophysical and nonlinear properties observed in the experiment can be perfectly replicated, our theoretical calculations explored the essential characteristics of the optical properties of the mesoionic compounds with different electron-donating groups at the level of electronic structures through various wave function analysis methods. The influence of the electron-donating ability of the donor on the optical properties of the molecules and the contribution of the mesoionic ring moiety to their optical nonlinearity are clarified, which have not been reported by any research so far. This work will help people understand the nature of optical properties of mesoionic-based molecules and provide guidance for the rational design of molecules with excellent photoelectric performance in the future.

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Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity

Molecules ◽

10.3390/molecules26113355 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3355

Author(s):

Matija Sambol ◽

Patricia Benčić ◽

Antonija Erben ◽

Marija Matković ◽

Branka Mihaljević ◽

...

Keyword(s):

Biological Activity ◽

Rational Design ◽

Human Cancer ◽

Photophysical Properties ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Quinone Methide ◽

Quantum Yields ◽

Photochemical Reactivity ◽

Human Cancer Cell Lines

Quinone methide precursors 1a–e, with different alkyl linkers between the naphthol and the naphthalimide chromophore, were synthesized. Their photophysical properties and photochemical reactivity were investigated and connected with biological activity. Upon excitation of the naphthol, Förster resonance energy transfer (FRET) to the naphthalimide takes place and the quantum yields of fluorescence are low (ΦF ≈ 10−2). Due to FRET, photodehydration of naphthols to QMs takes place inefficiently (ΦR ≈ 10−5). However, the formation of QMs can also be initiated upon excitation of naphthalimide, the lower energy chromophore, in a process that involves photoinduced electron transfer (PET) from the naphthol to the naphthalimide. Fluorescence titrations revealed that 1a and 1e form complexes with ct-DNA with moderate association constants Ka ≈ 105–106 M−1, as well as with bovine serum albumin (BSA) Ka ≈ 105 M−1 (1:1 complex). The irradiation of the complex 1e@BSA resulted in the alkylation of the protein, probably via QM. The antiproliferative activity of 1a–e against two human cancer cell lines (H460 and MCF 7) was investigated with the cells kept in the dark or irradiated at 350 nm, whereupon cytotoxicity increased, particularly for 1e (>100 times). Although the enhancement of this activity upon UV irradiation has no imminent therapeutic application, the results presented have importance in the rational design of new generations of anticancer phototherapeutics that absorb visible light.

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Tyrosine-protein kinase Src regulates Kv1.5 channel activity and membrane expression through interaction with the N-terminus of the channel

Inquiry@Queen's Undergraduate Research Conference Proceedings ◽

10.24908/iqurcp.14024 ◽

2020 ◽

Author(s):

Taylore Dodd ◽

Tingzhong Wang ◽

Shetuan Zhang

Keyword(s):

Protein Kinase ◽

Cell Voltage ◽

Underlying Mechanism ◽

Delayed Rectifier ◽

Binding Motif ◽

Membrane Expression ◽

Binding Motifs ◽

Delayed Rectifier Potassium Current ◽

N Terminus ◽

Tyrosine Protein Kinase

Kv1.5 is a voltage-gated potassium channel that generates the ultra-rapid delayed rectifier potassium current (IKur) important in the repolarization of the atrial action potential. Malfunction of the Kv1.5 channel often results in atrial fibrillation (AFib). A reduction in Kv1.5 current (IKv1.5) occurs upon activation of the endogenous tyrosine-protein kinase Src. The Src SH3 domain binds to proline-rich motifs located within the N-terminus of Kv1.5. Disruption of these binding motifs has been involved in the development of familial AFib. The mechanism underlying the reduction of IKv1.5 upon Src activation has not yet been established and the relationship between Kv1.5 and Src is poorly understood. Therefore, the present study aims to further elucidate the mechanism behind IKv1.5 reduction. The hypothesis that Src regulates Kv1.5 activity by altering the density of mature membrane-localized channels was tested using whole-cell voltage clamp and Western blot analysis. We demonstrate that Src tonically inhibits Kv1.5 activity and decreases the density of mature membrane-localized channels. Kv1.5 channels possessing mutations within the Src binding motifs were also investigated and it was determined that each binding motif contributes to the Kv1.5-Src relationship, however, the binding of Src to an individual motif is sufficiently effective. Our findings indicate that Src regulates Kv1.5 through an interaction with the N-terminal binding motifs and suggests that the inhibition of forward trafficking may be involved in the underlying mechanism. (Supported by the Heart and Stroke foundation of Canada and The Canadian Institutes of Health Research).

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Single-Particle Identification of Encoded Nanospheres

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057109356806 ◽

2010 ◽

Vol 15 (2) ◽

pp. 218-223 ◽

Cited By ~ 1

Author(s):

Hendrik Hippchen ◽

Wiebke H. Pohl ◽

Peter J. Walla

Keyword(s):

Single Particle ◽

Correlation Spectroscopy ◽

Particle Identification ◽

Carbohydrate Binding ◽

Binding Affinities ◽

Focal Volume ◽

Receptor Ligand ◽

Ligand Interactions ◽

Particle Level ◽

20 Nm

Recently, it has been shown that 2-photon fluorescence correlation spectroscopy of single glycosylated 20-nm fluorescent spheres allows measurement of the relative carbohydrate binding affinities of unlabeled proteins and that these modified spheres can mimic the glycocalix of cell or virus surfaces. An especially useful extension would be the analysis of mixtures of nanospheres that each contain different fluorescent labels and are thus differentially “encoded.” If the surfaces of these encoded nanospheres are modified with various receptors, many different biomolecule-surface interactions and concurrent reactions can be measured quickly and simultaneously in a single-reaction vessel. An essential prerequisite for this general assay principle is the ability to identify with an accuracy of nearly 100% any encoded nanosphere present in a mixture on a single-particle level. Here the authors present a method that indeed allows certain identification of differently encoded nanospheres during single transits through the focal volume of a microscope objective (ø~200-500 nm) in aqueous solution. This opens the way for using the encoded nanospheres in 1-well measurements of a large variety of biomolecular receptor-ligand interactions, inhibition and concurrent reactions, and thus either for testing the behavior of ligands in a mimicked complex biomolecular environment or for a fast simultaneous measurement of a multitude of receptor-ligand interactions.

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Structural modification strategies for the rational design of red/NIR region BODIPYs

Chemical Society Reviews ◽

10.1039/c4cs00030g ◽

2014 ◽

Vol 43 (13) ◽

pp. 4778-4823 ◽

Cited By ~ 692

Author(s):

Hua Lu ◽

John Mack ◽

Yongchao Yang ◽

Zhen Shen

Keyword(s):

Rational Design ◽

Structural Modification ◽

Photophysical Properties ◽

Structure Property ◽

Structure Property Relationships

The structure–property relationships of red/NIR region BODIPY dyes is analyzed, so that trends in their photophysical properties can be readily compared.

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Fluorescence correlation spectroscopy: The technique and its applications in soft matter

Physical Sciences Reviews ◽

10.1515/psr-2017-0104 ◽

2018 ◽

Vol 4 (4) ◽

Author(s):

Anjali Gupta ◽

Jagadish Sankaran ◽

Thorsten Wohland

Keyword(s):

Single Molecule ◽

Fluorescence Correlation Spectroscopy ◽

Soft Matter ◽

Photophysical Properties ◽

Spatiotemporal Analysis ◽

Correlation Spectroscopy ◽

Basic Principles ◽

Chemical Reaction Kinetics ◽

Fluorescence Correlation ◽

Wide Range

Abstract Fluorescence correlation spectroscopy (FCS) is a well-established single-molecule method used for the quantitative spatiotemporal analysis of dynamic processes in a wide range of samples. It possesses single-molecule sensitivity but provides ensemble averaged molecular parameters such as mobility, concentration, chemical reaction kinetics, photophysical properties and interaction properties. These parameters have been utilized to characterize a variety of soft matter systems. This review provides an overview of the basic principles of various FCS modalities, their instrumentation, data analysis, and the applications of FCS to soft matter systems.

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Effective Monofunctional Azaphthalocyanine Photosensitizers for Photodynamic Therapy

Australian Journal of Chemistry ◽

10.1071/ch08392 ◽

2009 ◽

Vol 62 (5) ◽

pp. 425 ◽

Cited By ~ 28

Author(s):

Petr Zimcik ◽

Miroslav Miletin ◽

Veronika Novakova ◽

Kamil Kopecky ◽

Marcela Nejedla ◽

...

Keyword(s):

Photodynamic Therapy ◽

Carboxy Group ◽

Rational Design ◽

Photophysical Properties ◽

Active Part ◽

Third Generation ◽

Highly Active ◽

Low Degree ◽

Band Absorption ◽

Group B

In this work we present a rational design of the active part of third generation photosensitizers for photodynamic therapy based on phthalocyanine and an azaphthalocyanine core. The preferred zinc complexes of the AAAB type that contain bulky tert-butylsulfanyl substituents (A) and one carboxy group (B) have been synthesized by statistical condensation and fully characterized. The tetramerization was performed using magnesium(ii) butoxide followed by demetalation and insertion of ZnII. Compound 1 synthesized from 4,5-bis(tert-butylsulfanyl)phthalonitrile (A) and 2,3-dicyanoquinoxaline-6-carboxylic acid (B) exerted very promising photophysical properties (Q-band absorption at 726 nm, ϵ = 140000 M–1 cm–1), which allowed strong absorption of light at long wavelengths where the penetration of the light through human tissues is deeper. The very high singlet oxygen quantum yield of 1 (ΦΔ = 0.80) assures efficient photosensitization. As a result of bulky peripheral substituents, compound 1 shows good solubility in organic solvents with a low degree of aggregation, which makes it potentially viable for non-complicated modification. One carboxy group in the final structure of 1 allows simple binding to possible carriers. This compound is suitable for binding to targeting moieties to form the highly active part of a third-generation photosensitizer.

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Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses

Cells ◽

10.3390/cells8101146 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1146 ◽

Cited By ~ 4

Author(s):

Brown ◽

del Corsso ◽

Zoidl ◽

Donaldson ◽

Spray ◽

...

Keyword(s):

Protein Transport ◽

Mutational Analysis ◽

Binding Motif ◽

Dependent Manner ◽

Electrical Synapses ◽

Binding Motifs ◽

Connexin 36 ◽

Dependent Transport ◽

Carboxy Terminal

Connexin-36 (Cx36) electrical synapses strengthen transmission in a calcium/calmodulin (CaM)/calmodulin-dependent kinase II (CaMKII)-dependent manner similar to a mechanism whereby the N-methyl-D-aspartate (NMDA) receptor subunit NR2B facilitates chemical transmission. Since NR2B–microtubule interactions recruit receptors to the cell membrane during plasticity, we hypothesized an analogous modality for Cx36. We determined that Cx36 binding to tubulin at the carboxy-terminal domain was distinct from Cx43 and NR2B by binding a motif overlapping with the CaM and CaMKII binding motifs. Dual patch-clamp recordings demonstrated that pharmacological interference of the cytoskeleton and deleting the binding motif at the Cx36 carboxyl-terminal (CT) reversibly abolished Cx36 plasticity. Mechanistic details of trafficking to the gap-junction plaque (GJP) were probed pharmacologically and through mutational analysis, all of which affected GJP size and formation between cell pairs. Lys279, Ile280, and Lys281 positions were particularly critical. This study demonstrates that tubulin-dependent transport of Cx36 potentiates synaptic strength by delivering channels to GJPs, reinforcing the role of protein transport at chemical and electrical synapses to fine-tune communication between neurons.

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